PML has been rearing its head again. It is the nemesis of Tysabri but as about 50% to 60% of MSers are infected with the virus that causes PML and it has to be a risk factor for anybody who is immunosuppressed.
Tysabri stops white bloodcells gettinginto the brain and so it cannot eliminate JC virus that maygetinto brain cells. If you don't have white blood cells in the blood it is also going to be a risk.
So why hasn't their being loads of PML in people taking interferon beta and copaxone? I suspect they are not very immunosuppressive.
So what about Alemtuzumab and Gilenya? Will they cause PML?
Quite possibly it is a numbers game. As more people use the drug for longer then the chances of this rare event increases.
However, PML appears to occur with long term immunosuppression and leucopaenia (Loss of white lood cells from the blood).
Whilst Alemtuzumab causes such long-term immunosuppression of the T cell response, it has to be said that Alemtuzumab will be out of the system within a month or so. After that people are drug free and therefore anti-viral cells can expand and do their job of getting rid of virus.
However with Gilenya you take it every day and it effectively empties the blood of white blood cells because they get stuck in the lymph glands and so shouldn't this have the risk seen with Tysabri?
There has been enough time for PML to have reared its head. It has of course but most of these have been following tysabri treatment.
However, it has to repeated that it is thought that Gilenya is not a blanket inhibitor of T cell function. It blocks naive (T cells that have not yet been stimulated by their target) and central memory cells (which is suggested to contain the population of cells that cause MS. It also hits a subset of memory B cells too) but not the Effector T cell population. It is this population that it has been suggested to contain viral immunity and so may give some protection against the JC virus. However of course this is not absolute as there have been problems of viral infections such as Herpes in people taking Gilenya but this bit of biology may contribute to the pausity so far of PML in people taking Gilenya.
CoI: None ProfG: multiple